By Jennifer Kahn
DISCOVER Vol. 26 No. 10 | October 2005

When Charlotte Benkner died last year at age 114, a dining hall in Ohio was named in her honor. Benkner, briefly acclaimed as the world's oldest living person, was known for eating a lot; one obituary listed her appetite as "voracious." It's enough to make the average person bitter: How could Benkner survive to truly old age on pork chops and cake when the rest of us may not make it to 70 without three servings of broccoli a day?

The answer lies in the fledgling science of nutritional genomics, the study of how our genes interact with the nutrients in the foods we eat. While a handful of food-gene interactions have been studied before-lactose intolerance, for instance, is known to be caused by a variation in the lactase gene-most are only now being charted.

"What constitutes good nutrition is actually a very individual prescription, depending on your particular set of genes," says Jose Ordovas, a biochemist at Tufts University who has studied the nutritional genomics of cardiovascular disease. In certain men, for instance, eating a low-fat diet may actually increase the risk of heart disease. This occurs because a polymorphism-a minor change in one gene-causes the person's LDL cholesterol level to rise when the amount of saturated fat in his or her diet drops too low.

50,000 women a year die during childbirth from severe iron deficiency 20 million infants a year are born mentally impaired due to iodine deficiency 200,000 severe birth defects annually are attributed to folate deficiency 40 percent of children under five in developing nations have compromised immune systems due to vitamin A deficiency

The average human has between 150,000 to 300,000 of these minor variations, known as single nucleotide polymorphisms, within individual genes. Together they are believed to account for most of the minor differences between people: variations in hair or eye color, metabolic rate, and one's susceptibility to such diseases as diabetes and osteoporosis. Many of these genes are activated by chemical triggers. Eat broccoli, for instance, and the vitamin B6 it contains will spur the tryptophan hydroxylase gene to produce L-tryptophan, an amino acid used in the synthesis of serotonin, a neurochemical mood stabilizer.

"The gene is the gun, but the environment is the finger on the trigger," says Ordovas. "These mutations have been with us for thousands, or in some cases hundreds of thousands of years, passing from one generation to the next, because until now our diet didn't trigger any negative effects."

Determining the effect of different nutrients on each gene variant is tricky and revolutionary because it would enable people to optimize their diet according to their particular genetics. Jim Kaput, a nutritional genomics researcher at the University of California at Davis and the University of Illinois at Chicago, notes that a percentage of the population has a polymorphic version of the GPDH gene, responsible for making an enzyme that helps cells convert sugar to energy.

The variation makes it harder for the enzyme to make use of niacin. As it turns out, the effects of this mutation could be offset fairly easily, simply by having people with that polymorphism eat more niacin. "This is an example of why nutrigenomics is so powerful," Kaput says. "Here's a case where, at least in theory, you can reverse the negative effects of a genetic polymorphism just by changing your multivitamin."

Few health problems are likely to be resolved so simply, of course. Even people who share the same polymorphism could react differently, depending on the rest of their genetic makeup. High blood pressure, for instance, has been linked to a polymorphism in the angiotensinogen gene that increases a person's sensitivity to salt. Tests exist that target the polymorphism, which crops up more frequently in certain populations. But not everyone with the mutation develops high blood pressure, and people without the mutation may also be susceptible.

The other challenge is identifying which nutrients interact with genes and how they do so. Resveratrol, found in red wine, grapes, blueberries, and peanuts, has been linked to some of the genes involved in longevity-but only in experiments done with yeast.

Blueberries have likewise been connected to better neurological health and slowed aging, perhaps because they contain antioxidants that make DNA more stable. So far, however, attempts to extract the single crucial nutrient have been unsuccessful.

"It's very difficult to come up with a silver bullet," says Ordovas. "Once we understand what combination of compounds are really providing the benefits-which nutrients stimulate the good genes and repress the bad genes-then we might be able to create some kind of ideal pill. What we're doing now, though, is practically guessing."

When these questions are eventually sorted out, the result, Ordovas says, will be a new science of personalized nutrition. "Eventually, we may go through a list of every single food and say, 'This is good for you, this is better for you.' " Fergus Clydesdale, a food scientist at the University of Massachusetts in Amherst, is even more bullish on the future: He predicts a day when we'll visit an online supermarket, input a color-coded genetic profile, and buy one of 10 different lasagnas, all of which taste the same but each of which has been made to fit a different nutrigenetic need. In the meantime, there's not much to do but sit tight and hope science discovers a gene that favors onion rings over kale.

THE VITAMIN GAP
Some 2 billion people in the world suffer vitamin and mineral deficiencies that can limit intellectual development, impair the immune system, cause birth defects, and hinder local economic growth. Here are a few vitamins on the global watch list.

 

DIALOGUE  GOT VITAMIN D? WALTER WILLETT is a professor of epidemiology and nutrition at the Harvard School of Public Health. He recently held a meeting of nutrition researchers to discuss widespread vitamin D deficiency in the United States. Why aren’t people getting enough vitamin D these days? W: Vitamin D is unusual in that we don’t get it from our food: We synthesize it by being out in the sun. But our whole cultural evolution has been to remove us from sunlight. We live in houses, drive cars, work inside, watchtelevision inside. In the northern part of the United States, even if you do go outside in the winter, the sun isn’t high enough on the horizon to activate the synthesis of vitamin D in the skin. Meanwhile, we’ve also realized that skin cancer can result from excessive radiation, so we’re now covering ourselves and putting on lotions to avoid sunburn. That further reduces the amount of vitamin D we can make. The truth is that we were made to run around in warm weather without our clothes on. Why are we only noticing this now? W: Actually, we realized that vitamin D deficiency was a problem 50 or 60 years ago, when children living in cities in the northern United States began to develop rickets. In response, a major public health program began adding vitamin D to milk. And that was pretty effective; it almost eliminated rickets from the United States. Now, cases of rickets are reemerging. Children’s Hospital in Oakland is seeing frequent incidences, usually in African American kids. Why is rickets coming back? W: As far as we can tell, it’s because the mothers who are breast-feeding children have very low levels of vitamin D themselves, so they can’t pass the vitamin along to their children. At a national level, African Americans have much lower vitamin D levels than most Caucasians. Doesn’t drinking more milk help? W: The recommended daily allowance for vitamin D is 400 international units—about what you get in a glass of milk. If you’re outside on a sunny day, though, you make almost 20,000 IUs. Four hundred is a drop in the bucket. It’s enough to prevent rickets, but that’s about it. Being just a little low on vitamin D can actually cause disease? W: Rickets is just the tip of the iceberg. Low vitamin D levels increase the risk of certain cancers, possibly multiple sclerosis as well, and possibly other conditions like asthma. Last year, a research group published a paper looking at vitamin D levels and future colon cancer risk. They found that the people who had the highest vitamin D levels had about half the rate of cancer, compared with people who had lower levels. When people migrate to Florida from the northeast, they actually reduce their risk of colon cancer. Some cancers are also particularly prevalent among African Americans—prostate cancer is one—and that may also be related to vitamin D.